In 1983 we reported the first successful treatment of non-24-hour sleep-wake syndrome (hypernychthemeral syndrome)-an apparently rare disorder. A second patient with this syndrome subsequently contacted us and we have elected to explore further the pathophysiology that may be responsible for the syndrome. Our goal is to employ a case study analysis of this patient's abnormality as a window into understanding various processes that control human circadian rhythms. We conducted a complete historical and hormonal "work-up" of the patient. The patient wore a light meter with computer-chip memory for a week to assess his level and pattern of ambient light exposure. The light meter was calibrated to measure ambient light with the sensitivity of the human eye. In a four-part set of circadian rhythm procedures the patient was admitted four times for assessment of sleep architecture, and 24 hour profiles of body temperature and various body hormones. Circadian hormone profiles were consistent with those of a "free-running" individual. Expected hour of sleep onset was delayed by two to three hours relative to the normal fall in temperature. We found significant abnormalities in the profiles of the patient's thyroid-related hormones, gonadal hormones, and melatonin. This case study-in-progress offers great potential for furthering our understanding of hormonal regulation of the sleep-wake cycle. We plan to explore the abnormal pineal gland and hypothalamic-pituitary-end organ axes in which we have already found abnormalities through endocrine challenge tests. We plan to try various pharmacological approaches to correct the sleep-wake disorder.